Neonatal intensive care units across the country are reporting with increasing frequency a syndrome of cyanosis and increased pulmonary vascular resistance (Persistence of the Fetal Circulation-PFC) of unknown etiology in term weight babies without congenital heart disease, pneumonia, or hyaline membrane disease. The present project is designed to provide a long-term animal study of this entity. Preliminary pilot studies undertaken this year have succeeded in producing an animal model of PFC in the newborn lamb. The lamb preparation is produced by chronic embolization of the placenta with non-radioactive micropheres beginning at 110 days gestation (term 150 days). Studies on experimental PFC lambs will include: pulmonary artery pressure; ascending and descending aortic pressures; left and right ventricular end diastolic pressures; and lung blood flow (by labeled microsphere technique). Relationship of hemodynamic parameter to: 1) the oxygen tension, 2) carbon dioxide tension, 3) pH, 4) blood glucose levels, 5) hematorcrit of the experimental lambs will be systematically evaluated. In addition we will measure the response of these same hemodynamic parameters to various drugs which are potential therapeutic agents in the disease: 1) tolazoline, 2) prostaglandin, 3) bradykinins, 4) antihistamines. Quantitative microscopic study of the muscular thickness of the pulmonary arteriolar wall is planned for PFC and control lambs. Finally, to separate the effects of CNS, hormonal, and metabolic influences from direct effect on the pulmonary vasculature of acidosis, oxygen, and pulmonary vasodilators, lungs from PFC lambs will be studied by isolated lung perfusion. Hemodynamic parameters and drug effects will be evaluation in this preparation.